Increased availability and consumption of ultra-processed foods have been associated with rising obesity prevalence, but past studies have not demonstrated whether ultra-processed food causes obesity or adverse health outcomes. We recently completed a clinical trial to investigate whether people ate more calories when exposed to a diet composed of ultra-processed foods compared with a diet composed of unprocessed foods (https://clinicaltrials.gov/ct2/show/NCT03407053). Despite the ultra-processed and unprocessed diets being matched for daily presented calories, sugar, fat, fiber, and macronutrients, we found that people consumed more calories when exposed to the ultra-processed diet as compared to the unprocessed diet. Furthermore, people gained weight on the ultra-processed diet and lost weight on the unprocessed diet. Therefore, our study results suggest that limiting consumption of ultra-processed food may be an effective strategy for obesity prevention and treatment. Competing theories about obesity and its treatment contrast the relative roles of dietary fat versus carbohydrate on promotion of excessive calorie intake. Proponents of low-fat diets argue that diets high in fat promote passive overconsumption due to the high energy density and low satiety index of high-fat foods. Advocates of low-carbohydrate diets propose that diets high in carbohydrates lead to elevated insulin secretion resulting in decreased energy expenditure and increased hunger. We recently tested the effects of a very low carbohydrate, ketogenic diet and found no meaningful effects on energy expenditure, but appetite and ad libitum calorie intake was not assessed. Therefore, we have initiated a feeding study (https://clinicaltrials.gov/ct2/show/NCT03878108) in 20 adult men and women to investigate the differences in ad libitum energy intake resulting from consuming two test diets for a pair of 2-week periods in a randomized, crossover design during a single 4-week inpatient period. The test diets presented to participants will be matched for calories and protein, but the low-carbohydrate diet (10% of calories) will be high in fat (75% of calories) whereas the low-fat diet will be high in carbohydrates (75% of calories) and low in fat (10% of calories).